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The multifaceted nature of αB-crystallin

  • PERSPECTIVES ON sHSPs
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

In vivo, small heat-shock proteins (sHsps) are key players in maintaining a healthy proteome. αB-crystallin (αB-c) or HspB5 is one of the most widespread and populous of the ten human sHsps. Intracellularly, αB-c acts via its molecular chaperone action as the first line of defence in preventing target protein unfolding and aggregation under conditions of cellular stress. In this review, we explore how the structure of αB-c confers its function and interactions within its oligomeric self, with other sHsps, and with aggregation-prone target proteins. Firstly, the interaction between the two highly conserved regions of αB-c, the central α-crystallin domain and the C-terminal IXI motif and how this regulates αB-c chaperone activity are explored. Secondly, subunit exchange is rationalised as an integral structural and functional feature of αB-c. Thirdly, it is argued that monomeric αB-c may be its most chaperone-species active, but at the cost of increased hydrophobicity and instability. Fourthly, the reasons why hetero-oligomerisation of αB-c with other sHsps is important in regulating cellular proteostasis are examined. Finally, the interaction of αB-c with aggregation-prone, partially folded target proteins is discussed. Overall, this paper highlights the remarkably diverse capabilities of αB-c as a caretaker of the cell.

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Abbreviations

αA-c:

αA-crystallin

αB-c:

αB-crystallin

ACD:

α-Crystallin domain

Aβ:

Amyloid beta

DLS:

Dynamic light scattering

FRET:

Förster resonance energy transfer

HMW:

High-molecular weight

IXI:

IXI motif

K d :

Dissociation constant

MS:

Mass spectrometry

PDB:

Protein Data Bank

RCM:

Reduced and carboxymethylated

R g :

Radius of gyration

R h :

Hydrodynamic radius

SANS:

Small-angle nuclear scattering

SAXS:

Small-angle X-ray scattering

sHsp:

Small heat-shock protein

UPP:

Ubiquitin-proteasome pathway

WT:

Wild type

γS-c:

γS-crystallin

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  1. Research School of Chemistry, The Australian National University, Acton, ACT, 2601, Australia

    Junna Hayashi & John A. Carver

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  1. Junna Hayashi
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  2. John A. Carver
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Correspondence to John A. Carver.

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Hayashi, J., Carver, J.A. The multifaceted nature of αB-crystallin. Cell Stress and Chaperones 25, 639–654 (2020). https://doi.org/10.1007/s12192-020-01098-w

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